NOTES
766
a t 140' and a flow rate of 55 cc. helium/niin. The estimated per cents of apocamphane and 1-bromoapocamphane were 22% and 78%, respectively. The per cents were estimated by comparison with standard chromatograms. Reduction of cis-a-Bromostilbene with Triphenyltin Hydride, Reduction No. 10.-.4 mixture of 5.18 g. (0.02 mole) of cis-abr~mostilbenez~ and 7.02 g. (0.02 mole) of triphenyltin hydride was stirred a t ca. 26". During 10 min. the reaction temperature rose to 42", remained a t this temperature for 5 min., and then gradually decreased t'o ca. 26". After 1 hr. the react,ion mixture had completely solidified. The mixture was allowed to remain a t ea. 26" overnight before processing. It was then slurried with 25 ml. of petroleum ether (b.p. 30-60") and poured onto 100 g. of Woelm neutral alumina (activity 1-11). The column was eluted with petroleum ether until 700 ml. of eluate was obtained. Distillation of the petroleurn ether in vucuo left 6.2 g. of solid material which was recrystallized from 95% ethanol to give 3.18 g. of trans-stilbene, m.p. 120-122', no depression on admixture with a known sample of trans-stilbene, infrared and ultraviolet, spectra superimposable on that of a known sample of trans-stilbene, The mother liquor was evaporated to dryness, slurried with 25 ml. of petroleum ether and poured onto 70 g. of Woelm neutral alumina (activity 1-11), The column was eluted with petroleum ether until 500 ml. of eluate was obtained. Evaporat,ion of the petroleum ether followed by recrystallization of the solid residue from !Elc? ethanol gave 350 mg. of trans-stilbene, m.p. 120-122", total yield of trans-stilbene 3.53 g. (98.0%). The first column (100 g. of alumina) was eluted with methylene chloride-methanol (9: 1) until 700 ml. of eluate was obtained, and the second column was eluted with methylene chloridemet,hanol (9: 1) until 500 ml. of eluate wa9 obtained. The two fractions were combined, and the solvent was distilled in vacuo. There remained 6.6 g. of solid material, m.p. 95-98', which upon recrystallizat,ion from n-propyl alcohol gave 6.35 g. (73.87,) of triphenyltin bromide, m.p. 116-118'. I n another run using 2.59 g. (0.01 mole) of cis-a-bromostilbene and 3.51 g. (0.01 mole) of triphenyltin hydride there was obtained, using essentially the same isolation procedure as above, transstilbene (88.8Yc) and triphenyltin bromide (72.1%). I n another run using 5.18 g. (0.02 mole) of cis-a-bromostilbene and 7.02 g. (0.02 mole) of triphenyltin hydride and carried out a t cis-stilca. 26 to 2Y0, there was obtained trans-stilbene (61.1 7c), bene (30.5%), and triphenyltin bromide (72.0%). Reduction of trans-a-Bromostilbene with Triphenyltin Hydride. Reduction No. ll.--A mixture of 7.0 g. (0.027 mole) of trans-abromostilbene24 and 9.47 g. (0.027 mole) of triphenyltin hydride was stirred a t ea. 26'. During the course of 10 min. the temperature rose to 30", remained a t that temperature for 15 min., and then returned to ca. 26'. After 24 hr. the reaction mixture had become a thick paste. The mixture was slurried with 25 ml. of petroleum ether and poured onto 70 g. of Woelm neutral alumina (activity 1-11, column I ) . The column was eluted withpetroleum ether. The first 250-ml. portion of eluate yielded no residue. The next two 500-ml. portions of eluate were combined and yielded, after removal of the solvent, 7.4 g. of a semisolid, which was slurried with 20 ml. of n-hexane and cooled overnight in a refrigerator. The crystals which were present were collected on a filter ( 1 . 6 5 g . ) , m.p. 112-114". Recrystallization from 95% ethanol gave 1.60 g. of trans-stilbene, m.p. 120-122', no depression on admixture with an authentic sample of trans-stilbene. The hexane was removed from the first mother liquor in vacuo, and the residue was distilled to give 1.87 g. (38.67,) of cis-stilbene, b.p. 93-97' (2 m m . ) : authentic cis-stilbene had b.p. 93-96' (2 mni.) . The infrared and ultraviolet spectra were superimposable upon that of an authentic sample of cis-stilbene. The residue from the distillation was slurried with 25 ml. of petroleum ether and poured onto 70 g.,of Woelm neutral alumina (activity 1-11, column 11). The column was eluted with petroleum ether until 250 ml. of eluate was obtained. Removal of the petroleum ether in vacuo gave 1.5 g. of a semisolid which yielded after two recrystallizations from 95CG ethanol 1.03 g. of transThe total yield of trans-stilbene was stilbene, m.p. 120-122'. 2.63 g. (54.17,). Column I was further eluted with methylene chloride-methanol (98:2) until 1 1. of eluate was obtained. Column I1 was eluted with methylene chloride-methanol (98:2) until 250 ml. of eluate was obtained. The two eluates were combined, and the solvent _ _ ~ ~ _ _ (24) J . FVislicenus, B c r . Verhandl. sachs. Akad. p h y s . K1.. 61, 117 (1900).
u'iss.
L e i p t z g Math.
VOL. 29
was removed in vacuo leaving 8.65 g. of solid material which afforded after recrystallization from n-propyl alcohol 8.32 g. (71.7 %) of triphenyltin bromide, m.p. 116-118". Separation of a Known Mixture of trans-Stilbene, cis-Stilbene, and Triphenyltin Bromide.--A known mixture consisting of 1.62 g. of trans-stilbene, 0.180 g. of cis-stilbene, and 4.30 g. of triphenyltin bromide was slurried with 25 ml. of petroleum ether and poured onto 70 g. of Woelm neutral alumina (activity 1-11). The column was eluted with petroleum ether until 500 ml. of eluate was obtained. Removal of the solvent in z'acuo left 1.85 g. of a semisolid which gave after recrystallization from 95% ethanol 1.55 g. of trans-stilbene, m.p. 120-122'. The mother liquor was evaporated to dryness, and the residue was dissolved in 5 ml. of hexane and allowed to stand a t -5" overnight. The crystals were collected on a filter giving 50 mg. of trans-stilbene, m.p. 120-122". The total yield of trans-stilbene was 1.60 g. (98.77,). Removal of the hexane from the filtrate followed by distillation of the residue gave 0.180 g. (100%) of czs-stilbene, b.p. 9396" (2 mm.). The column was further eluted with methylene chloridemethanol (9: 1) until 500 ml. of eluate was obtained. Removal of the solvent in vacuo left 3.4 g. of solid material which afforded after recrystallization from n-propyl alcohol 3.4 g. (79.07,) of triphenyltin bromide, m.p. 116-118".
The Absolute Configuration of Citrinin' RICHARD K. HILLASD LIBEROA. GARDELLA Prick Chemical Laboratory, Princeton University, Princeton, ~YewJersey Received September 23, 1963
One of the first compounds wit,h antibiotic activity isolated in Raistrick's classic investigations on fungal metabolites was the substance citrinin, obtained in 1931 from Penicillium citrinum.2 Though it proved too toxic for medical use, the discovery of it's activity intensified the search which subsequently led to practical antibiotics. The structure of citrinin (I) was established in 1949, primarily by the investigations of Robertson and his co-workers, and several syntheses have been re~ o r d e d . An ~ ingenious suggestion of Cram5 led to the assignment of relative stereochemistry. Hydrolysis of citrinin gives the levorotatory phenol (11) which is partially or wholly racemized by acid. Cram pointed out that if the methyl groups on the asymmetric carbons of citrinin were trans, participation of the aromat'ic ring in the formation of a carbonium ion from I1 would afford a symmetrical intermediate and consequently lead to racemization ; his subsequent studies wit'h model compounds confirmed this proposaL6 Further degradation of citrinin has now made it possible to complete the stereochemical assignment by showing the absolute configuration. The dimethyl (1) This investigation was supported by a research grant ( G M 065G8-04) from the Public Health Service, t o whom the authors express their appreciation. (2) .4.C. Hetherington and H. Raistrick, Phil. Trans, Roy. SOC.London. 11OB,269 (1931). (3) (a) J. P. Brown, K. J. Cartwright, A . Robertson, and W.B. Whalley. J . Chem. Soc., 859 (1949); (b) J. P. Brown, A . Robertson, W . B. Whalley, and S . J. Cartwright. i b i d . , p. 867. (4) (a) N. J. Cartwright, A. Robertson, and W. B. Whalley. ibid., 1.563 (1949); (b) H. H. Warren, G. Dougherty, and E. S.Wallis. J . A m . Chem. Soc., 71, 3422 (1919); (e) T. 5 . Gore, R. V. Talavdekar. and K . Venkataraman, Curvent Sci. (India), 19, 20 (1950); Chem. Abstr., 44, 7313 (1950). ( 5 ) D. J. Cram, J . A m . C h e n . Soc.. 7 0 , 4244 (1948). ( 6 ) D. J . Cram, t b t d . , 71, 3883 (1949): 72, 1001 (1950).
NOTES
~VARCH, 1964
767
formula I as the correct expression of absolute stereochemistry of ~ i t r i n i n . ~ Experimental
-10
-20
-30
Cil -40 -50
-60
I
I I I
I
I
400
A! w
I
1
500
I
600
Fig. 1.-O.R.D. curves (chloroform) of 2-(2-methyl-3,5-dimethoxypheny1)butane (F’) and 2-phenylbutane (VI).
OH
OR
( - )-2-(3,5-Dimethoxy-2-methylphenyl)butane (V).-To a solution of 13.3 g. of 3-(3,.5-dimethoxy-2-methyIphenyl)butan-2-01 (111, “phenol A dimethyl ether”)3ain 150 ml. of pyridine, cooled to O ” , 15.25 g. of p-toluenesulfonyl chloride was added slowly with stirring, and the mixture was kept in the refrigerator for 48 hr. The reaction mixture was poured onto 500 g. of ice and water and was extracted with ether; the ether extracts were washed with cold 1 : 1 hydrochloric acid, then with water, dried, and concentrated a t reduced pressure. The residual oily tosylate was not purified further hut showed characteristic sulfonate bands in the infrared at 7.4 and 8.5 along with the complete lack of hydroxyl absorpt,ion. A solution of the tosylate in 175 ml. of anhydrous ether was added dropwise to a stirred suspension of 2.75 g. of lithium aluminum hydride in 100 ml. of ether, and the reaction mixture refluxed for 12 hr. The excess hydride was decomposed with dilute sodium hydroxide, and the mixture was filtered. The ether layer, after washing with dilute base and water, was dried and distilled, affording 10.9 g. (80%) of V, b.p. 91.5-93’ (0.5 mm.), [ . Y ] ~ ’ D -8.70” ( c 10, chloroform). Anal. Calcd. for C13H2002: C, 74.96; H, 9.68. Found: C, 75.19; H, 9.46. The infrared spectrum, in rhloroform, was identical with that of authentic racemic material.3a (-)-2-Phenylbutane (VI).-An authentic sample of the hydrocarbon was obtained. by hydrogenation of ( - )-3-phenyl-1 ~ O D -7.36” (chloroform), over palladium-charcoal butene,’O [a] in methanol. The product had [ C Y ] ~ ~ D14.2” ( c 10, chloroform).
Acknowledgment.-The authors wish to thank Dr. Erwin Schwenk for a generous gift of citrinin. (9) Recently the same conclusion has been independently reached by P. P. Mehta and W. B . Whalley, J. Chem. Soc., 3777 (1963). (10) D. J. Cram, J . Am. Chem. Soc., 74, 2137 (1952). The authors wish to thank Dr. M .Rabinovitz for supplying this material.
I
Elimination Reactions. IV. Phenylspiropentane by y-Elimination
R
R &CH&& R‘CHsH
v, R = O C H s ; R’=CHa VI, R - R ’ =
H
ether (111) of the phenol I1 was converted to its p-toluenesulfonate (IV) . Lithium aluminum hydride reduction of the tosylate gave the levorotatory ether (V), with only one asymmetric carbon. Though there is no guarantee of the optical purity of V, since partial racemization could occur during reduction’ via the same symmetrical phenonium ion which participates in the acid hydrolysis of citrinin, its optical rotation is sufficient to establish its configuration by optical rotatory dispersion measurements. Comparison of the O.R.D. curves of (-)-V and (-)-2-phenylbutane (VI), shown in Fig. I, clearly proves their configurational identity.8 Since the configuration of ( - )-2-phenylbutane has been proven to be that shown in VI,’’ this result establishes the configuration shown in (7) (a) D . J. Cram, J . Am. Chem. S o c . , 74, 2149 (1952); (b) 74, 2152 (1952). (8) For evidence that simple aryl substituents do not change the general shape of the O.R. D. curves of aromatic compounds, see (a) J . H. Brewster and S . F. Qsman. ibid., 81, 5754 (1960); (b) F. Nerdel and H. Harter, Ann., 641, 22 (1959); (c) F. Nerdel and H. WUrgau, ibid., 641, 34 (1959); (d) F. Nerdeland H . Liebig, ibid., 641, 42 (1959).
CARLL. BUMQARDKER
Goryas Laboratory, Rohm and Haas Company, Redstone Arsenal Research Division, Huntsville, Alabama Received September 23, 1963
Treatment of a number of 3-phenylpropylamine derivatives with sodium amide in liquid ammonia has been found to produce phenylcyclopropanes via yelimination.’ To extend the scope of this reaction we synthesized methiodide I where the p-carbon atom is incorporated into a three-membered ring. Structure I also provided an additional opportunity to study the behavior of carbanions generated adjacent to a small ring.2 Reaction of quaternary salt I with sodium amide in liquid ammonia led exclusively to the 7-elimination product phenylspiropentane (11) which was isolated in about 50% yield. Assignment of structure I1 follows from analysis of the n.m.e spectrum. Signals are observed a t 7.1 (5 protons), 2.2 (1 proton, a quartet), 1.4 (I proton, a quartet), and 0.9 p.p.m. ( 5 protons, (1) C. L. Bumgardner, J. A n . Chem. S o c . , 83, 4420 (1961); 83, 4423 (1981). (2) C. L. Bumgardner, zbzd., 88, 73 (1963).
